Figure 2.
Blocking anti-GARP:TGF-β1 mAbs reduces fibrosis and tumor burden in murine PMF. MPLW508A and MPLWT control mice, generated as indicated in Figure 1, were injected IP weekly with the indicated mAbs, starting 1 day before transplantation of the transduced BM cells (n = 8-10 mice per group). C57BL/6 mice that did not undergo transplantation served as additional controls (ctrl). Blood was taken on day 28 and mice were euthanized on day 34 to collect femurs and spleens. (A) Histological assessment of fibrosis in sections of paraffin-embedded spleens and femurs after silver staining. Representative sections are shown on the left. Fibrosis scores, corresponding to reticulin staining grades expressed on a modified Bauermeister scale,28 are indicated on the right. Data points: scores in individual mice; horizontal bars: mean + SEM per group. (B) Blood cell counts and GFP expression were determined using a hematological analyzer and flow cytometry. Data points on the left: blood cell counts in individual mice; horizontal bars: mean + SEM per group. Stacked bar graphs on the right: mean + SEM of GFP+ and GFP- cells. Data from 1 of at least 4 independent experiments. P values calculated using a two-tailed Student t test. SEM, standard error of the mean.